More research is needed on seriously mentally ill smokers, who, to date, have been under-studied and suffer disproportionate tobacco use and disease. This proposal responds to an NIMH Program Announcement (PA-05-019) and is consistent with a recent NIMH workgroup on Tobacco Use and Cessation in Psychiatric Disorders which concluded that significant advances in treating smokers with schizophrenia might not occur until there is better understanding of the role of nicotine in the context of the mental disorder. Individuals with schizophrenia are heavy smokers with only half the success in making a quit attempt as other smokers. Preliminary evidence, including our own, indicates that smokers with schizophrenia have higher nicotine levels than control smokers who smoke the same number of cigarettes per day. This is presumed to be an increase in nicotine intake which is due to differences in cigarette puffing behavior although studies have not confirmed this. The emphasis of this proposal is to conduct two studies of cigarette puffing behavior and nicotine intake in smokers with schizophrenia and compare these results to 2 control groups: smokers without mental illness and smokers with bipolar disorder. We expect that smokers with schizophrenia will have a higher nicotine intake per cigarette, also termed "nicotine boost", compared to controls. We also expect that smokers with schizophrenia will differ in smoking topography measures with decreases in inter-puff interval (IPI, the time between puffs) compared to controls. In Study #1 we will recruit 300 smokers (100 with schizophrenia, 100 with bipolar disorder and 100 controls without mental illness) in order to measure nicotine intake and smoking topography on a usual smoking day. Subjects will participate in three blood draws and a smoking topography session during ad lib smoking from 6am to 3pm. In Study #2 we will measure nicotine boost from a single cigarette in a laboratory based design using repeated blood measures in a subgroup of 30 smokers from Study #1. This study allows us to precisely measure the nicotine peak and also characterize nicotine blood levels in the first hour after smoking to measure the total nicotine dose from a single cigarette. Understanding differences in nicotine boost has important implications for the type of nicotine replacement medications which may prove be most effective for this group and is an important step in the development of better pharmacological treatments. [unreadable] [unreadable] [unreadable]